This paper presents the preparation of novel thiacalixarene (TCA) covalently functionalized multi-walled carbon nanotubes (MWCNTs), and an enhanced differential pulse anodic stripping voltammetric procedure for the determination of trace amounts of Pb2+ ions, which relies on the selective accumulation of the metals at a TCA-MWCNT-modified glassy carbon electrode. Through a combination of thiacalixerene's excellent selective recognition and the outstanding electronic properties of MWCNTs, this electrode material shows excellent selectivity and high sensitivity for electrochemical detection of Pb2+ ions. The stripping response is highly linear (R=0.999) over a Pb2+ concentration range of 2×10-10 to 1×10-8 mol/L, and the limit of detection is 4×10-11 mol/L. Furthermore, the determination of Pb2+ (10-7 mol/L) in the presence of an equal amount of interfering Sn2+ ions yielded well-separated signals. To understand the molecular interaction mechanism between the TCA molecules and metal ions (Pb2+ and Sn2+), theoretical computations were performed. The results demonstrate that the Pb2+/Sn2+ ions could stably adsorb onto the TCA molecules and there is significant electron delocalization between Pb2+/Sn2+ and sulfur atoms in the TCA molecule.